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This study aimed to design and synthesize 28 novel derivatives of 7-aryl-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one. The derivatives were created from 7-bromoquinoline intermediates to evaluate their potential as cholinesterase inhibitors for treating neurodegenerative diseases such as Alzheimer\u2019s disease. The conditions for the Suzuki\u2013Miyaura cross-coupling reaction were optimized to improve yield and purity. The derivatives were evaluated for their anticholinesterase activity using Ellman\u2019s method, revealing that it most effectively inhibited cholinesterase within the micromolar range. 7-(3-Chloro-4-fluorophenyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one derivative exhibited the highest inhibitory potency, with an IC50 value of 6.084 \u00b1 0.26 \u03bcM. Additionally, molecular dynamics simulations provided insight into how this lead compound interacts with the enzyme, suggesting its potential as a drug candidate for Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.3390\/molecules30132791","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T11:37:51Z","timestamp":1751283471000},"page":"2791","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Synthesis of Novel 7-Phenyl-2,3-Dihydropyrrolo[2,1-b]Quinazolin-9(1H)-ones as Cholinesterase Inhibitors Targeting Alzheimer\u2019s Disease Through Suzuki\u2013Miyaura Cross-Coupling Reaction"],"prefix":"10.3390","volume":"30","author":[{"given":"Davron","family":"Turgunov","sequence":"first","affiliation":[{"name":"Department of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifei","family":"Nie","sequence":"additional","affiliation":[{"name":"State Key Laboratory Basis of Xinjiang Indigenous M\u00edicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Rd 40-1, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azizbek","family":"Nasrullaev","sequence":"additional","affiliation":[{"name":"Department of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zarifa","family":"Murtazaeva","sequence":"additional","affiliation":[{"name":"Department of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianlin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory Basis of Xinjiang Indigenous M\u00edicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Rd 40-1, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilafruz","family":"Kholmurodova","sequence":"additional","affiliation":[{"name":"Scientific and Practical Center of Immunology, Allergology and Human Genomics, Samarkand State Medical University, Makhdum-i A\u02bf\u1e93am st. 18, Samarkand 140104, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rustamkhon","family":"Kuryazov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Urgench State University, Kh. Olimjon st. 14, Urgench 220100, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory Basis of Xinjiang Indigenous M\u00edicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Rd 40-1, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7449-0936","authenticated-orcid":false,"given":"Khurshed","family":"Bozorov","sequence":"additional","affiliation":[{"name":"Department of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan"},{"name":"State Key Laboratory Basis of Xinjiang Indigenous M\u00edicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Rd 40-1, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4652-6879","authenticated-orcid":false,"given":"Haji Akber","family":"Aisa","sequence":"additional","affiliation":[{"name":"State Key Laboratory Basis of Xinjiang Indigenous M\u00edicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Rd 40-1, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104057","DOI":"10.1016\/j.drudis.2024.104057","article-title":"Pharmaceutical innovation and advanced biotechnology in the biotech-pharmaceutical industry for antibody\u2013drug conjugate development","volume":"29","author":"Ma","year":"2024","journal-title":"Drug Discov. 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